Ultrasensitive sensors reveal the spatiotemporal landscape of lactate metabolism in physiology and disease

Cell Metab. 2023 Jan 3;35(1):200-211.e9. doi: 10.1016/j.cmet.2022.10.002. Epub 2022 Oct 28.

Abstract

Despite its central importance in cellular metabolism, many details remain to be determined regarding subcellular lactate metabolism and its regulation in physiology and disease, as there is sensitive spatiotemporal resolution of lactate distribution, and dynamics remains a technical challenge. Here, we develop and characterize an ultrasensitive, highly responsive, ratiometric lactate sensor, named FiLa, enabling the monitoring of subtle lactate fluctuations in living cells and animals. Utilizing FiLa, we demonstrate that lactate is highly enriched in mammalian mitochondria and compile an atlas of subcellular lactate metabolism that reveals lactate as a key hub sensing various metabolic activities. In addition, FiLa sensors also enable direct imaging of elevated lactate levels in diabetic mice and facilitate the establishment of a simple, rapid, and sensitive lactate assay for point-of-care clinical screening. Thus, FiLa sensors provide powerful, broadly applicable tools for defining the spatiotemporal landscape of lactate metabolism in health and disease.

Keywords: highly responsive lactate sensors; lactate metabolism; point-of-care clinical screening; real-time monitoring; subcellular lactate landscape.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental* / metabolism
  • Lactic Acid / metabolism
  • Mammals
  • Mice
  • Mitochondria / metabolism

Substances

  • Lactic Acid